Association of the AGXt2 V140i polymorphism with risk for coronary heart disease in a Chinese population

Abstract

Aim: Asymmetric dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor that decreases NO production and promotes the development of cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) plays an important role in ADMA metabolism. This study was designed to explore the association of the AGXT2 V140I (rs37369 G＞A) polymorphism with risk for coronary heart disease (CHD) in a Chinese population. Methods: A case-control study including 1103 controls and 942 CHD patients was performed. The patients were genotyped for rs37369 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma ADMA concentration in healthy controls was measured by an enzyme-linked immunosorbent assay (ELISA). Results: The rs37369 GG genotype was significantly overrepresented in CHD patients compared to the controls (18.5% versus 14.8%, p= 0.025), and it was significantly associated with increased risk for CHD in smokers (OR= 2.21, 95% CI: 1.24-3.92, p= 0.007) and marginally increased CHD risk for individuals with diabetes mellitus (OR = 1.92; 95% CI: 0.94-3.91, p= 0.074). The association between rs37369 and CHD risk was further increased in smokers with diabetes mellitus (OR = 3.32, 95% CI:1.14-9.67, p = 0.028). Patients who smoked and were rs37369 GG homozygous showed significantly higher plasma ADMA levels than carriers of the rs37369 A allele (p = 0.004). However, in non-smokers, patients homozygous for rs37369 GG showed significantly lower plasma ADMA concentrations than carriers of the rs37369 A allele (p = 0.003). Furthermore, smokers homozygous for rs37369 GG showed significantly higher plasma ADMA concentrations than non-smokers with the same genotype (p = 0.012). Conclusion: The AGXT2 rs37369 polymorphism is associated with increased risk for CHD in smokers and in diabetes mellitus patients. This increased risk may be due to increased plasma ADMA levels.